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The blood-brain barrier (BBB) breakdown has been suggested as an early marker for Alzheimer's disease (AD); yet the relationship between BBB breakdown and AD-specific biomarkers based on the amyloid/tau/neurodegeneration framework is not clear. This study investigated the relationship between BBB permeability, AD-specific biomarkers, and cognition in patients with cognitive impairment. In this prospective study, we enrolled 62 participants with mild cognitive impairment or dementia between January 2019 and October 2020. All participants were assessed through cognitive tests, amyloid positron emission tomography (PET), dynamic contrast-enhanced magnetic resonance imaging (MRI) for BBB permeability (Ktrans), cerebrospinal fluid studies for Aβ42/40 ratio, phosphorylated-tau Thr181 protein (p-tau), total tau protein (t-tau), and structural MRI for neurodegeneration. In amyloid PET (+) group, higher cortical Ktrans was associated with lower Aβ40 (r = −0.529 p = 0.003), higher Aβ42/40 ratio (r = 0.533, p = 0.003), lower p-tau (r = −0.452, p = 0.014) and lower hippocampal volume (r = −0.438, p = 0.017). In contrast, cortical Ktrans was positively related to t-tau level. (r = 0.489, p = 0.004) in amyloid PET (−) group. Our results suggest that BBB permeability is related to AD-specific biomarkers, but the relationship can vary by the presence of Aβ plaque accumulation. [ABSTRACT FROM AUTHOR]

Background and Purpose: Apolipoprotein E4 (APOE4) is a major genetic risk factor for Alzheimer's disease. However, the effect of APOE4 status on myelin remains unclear. This study investigated the effect of APOE4 on myelin content in cognitively impaired individuals using T2* gradient echo (GRE)‐based myelin water fraction (MWF) imaging. Methods: Between August 2017 and January 2019, we evaluated 39 cognitively impaired patients (median age, 75 years; male:female = 8:31; Alzheimer's disease: mild cognitive impairment = 11:28). We obtained brain MWF values from white matter hyperintensities (WMHs) and normal‐appearing white matter (NAWM). Linear regression analysis was performed to investigate the relationship between the APOE4 status and MWF and cognitive function and MWF. Results: Among the 39 cognitively impaired patients, nine (23.1%) were APOE4 carriers and 30 (76.9%) were noncarriers. APOE4 carriers had a lower hippocampal volume than noncarriers (p =.045), but other brain volume parameters were not differed. After age adjustment, the APOE4 status was significantly associated with reduced MWF in NAWM (β = –0.310 per allele; p =.049) but not in WMH (β = –0.258 per allele; p =.113). After age adjustment, MWF in NAWM was significantly associated with Mini‐Mental State Examination score (β = 0.313, p =.031). Conclusions: T2* GRE‐based MWF imaging can reveal myelin loss, particularly in NAWM, in cognitively impaired patients among APOE4 carriers. In vivo MWF in NAWM might be a novel imaging marker of Alzheimer's disease, for clarifying the interactions between the white matter and cognitive dysfunction with respect to the APOE4 status. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) disruption, modulated by APOE4 mutation, is implicated in the pathogenesis of cognitive decline. We determined whether BBB permeability differed according to cognitive functioning and APOE4 status in elderly subjects without dementia. In this prospective study, 33 subjects with mild cognitive impairment (MCI) and 33 age-matched controls (normal cognition [NC]) underwent 3 T brain magnetic resonance imaging. The Patlak model was used to calculate tissue permeability (Ktrans). A region-of interest analysis of Ktrans was performed to compare relevant brain regions. Effects of Ktrans on cognitive functioning were evaluated with linear regression analysis adjusted for confounding factors. NC and MCI groups did not differ in terms of vascular risk factors or hippocampal Ktrans, except for hippocampal volume. Hippocampal Ktrans was significantly higher in APOE4 carriers than in non-carriers (p = 0.007). Factors which predicted cognitive functioning included hippocampal volume (beta=−0.445, standard error [SE]=0.137, p = 0.003) and hippocampal BBB permeability (beta = 0.142, SE = 0.050, p = 0.008) after correcting for age, education, and APOE4 status. This suggests that hippocampal BBB permeability is associated with APOE4 mutation, and may predict cognitive functioning. BBB permeability imaging represents a distinct imaging biomarker for APOE4 mutations in NC and MCI subjects and for determining the degree of APOE4-related pathology. [ABSTRACT FROM AUTHOR]

Introduction: Many factors are known to affect the rate of cognitive decline; however, studies on clinical outcomes are rare. Muscle profile and their relationship to dementia trajectories have not been extensively investigated. We investigated factors that affect the rate of clinical decline and the usefulness of muscle profiles for predicting the clinical outcomes of patients with Alzheimer's dementia (AD). Objective: Sixty-nine subjects with probable AD were included and several factors that are known to affect the rate of cognitive decline were evaluated. Methods: Over a period of 3 years, each subject received an annual evaluation that included a clinical interview and an assessment of their cognitive status as measured by a clinical dementia rating-sum of boxes (CDR-SOB) score. Linear mixed-effects models were used to test for associations between each factor and the -CDR-SOB score over time. These analyses were repeated in a multivariate linear mixed-effects model after adjusting the covariates. Results: Age, diabetes mellitus, and baseline dementia severity were identified as potential covariates that influence clinical progression. However, a subject's muscle profile was not found to predict dementia progression. Conclusions: We expect that early screening and intervention, as well as new drugs with mechanisms of action similar to those of antidiabetic medications, will help patients with dementia maintain their clinical status. [ABSTRACT FROM AUTHOR]

Background/Aims: Alzheimer's disease (AD) is the most common cause of dementia worldwide. Interestingly, muscle mass (MM) and muscle strength (MS) are related to AD. In addition to the muscle profile, brain atrophy is also a prominent feature of AD. There is substantial evidence showing an association between muscle profile and dementia, but the role of the muscle profile and cerebral cortical atrophy within this association is less well understood. The objective of this study was to determine if there is any association between muscle profile and brain regional volume in AD. A secondary objective was to determine whether this relationship continues as the clinical stage of AD progresses. Methods: We recruited 28 patients with probable AD without weakness. We assessed the patients' basic demographic characteristics, Mini-Mental State Examination score, and brain magnetic resonance images. MM was measured using body dual-energy X-ray absorptiometry. MS was assessed in Nm/kg with an isokinetic knee extensor using an isokinetic device at an angular velocity of 60°/s. An automatic analysis program was used for brain regional volumetric measurements. Dementia was divided into two stages: mild and moderate. Results: MS was related to left hippocampal volume ratio. After adjusting for age and cognitive status, the relationship remained. MS did not demonstrate any relationship to any brain regional volume ratio in the mild stage; however, in the moderate stage, it was positively related to both the right and the left hippocampal volume ratio. Conclusions: Our findings imply a shared underlying pathology relating MS and brain volume and suggest cognitive functional declines through the muscle-brain axis. Further longitudinal studies are needed to find possible and related causes of reduced MS and cortical atrophy in patients with dementia. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that diabetes mellitus (DM) is associated with iron and calcium metabolism. However, few studies have investigated the presence of DM in cognitively impaired patients and its effect on brain iron and calcium accumulation. Therefore, we assessed the effects of DM on cognitively impaired patients using quantitative susceptibility mapping (QSM). From June 2012 to Feb 2014, 92 eligible cognitively impaired patients underwent 3T magnetic resonance imaging (MRI). There were 46 patients with DM (DM+) and 46 aged matched patients without DM (DM-). QSM was obtained from gradient echo data and analyzed by drawing regions of interest around relevant anatomical structures. Clinical factors and vascular pathology were also evaluated. Measurement differences between DM+ and DM- patients were assessed by t tests. A multiple regression analysis was performed to identify independent predictors of magnetic susceptibility. DM+ patients showed lower susceptibility values, indicative of lower brain iron content, than DM- patients, which was significant in the hippocampus (4.80 ± 8.31 ppb versus 0.22 ± 10.60 ppb, p = 0.024) and pulvinar of the thalamus (36.30 ± 19.88 ppb versus 45.90 ± 20.02 ppb, p = 0.023). On multiple regression analysis, microbleed number was a predictor of susceptibility change in the hippocampus (F = 4.291, beta = 0.236, p = 0.042) and DM was a predictor of susceptibility change in the pulvinar of the thalamus (F = 4.900, beta = - 0.251, p = 0.030). In cognitively impaired patients, presence of DM was associated with lower susceptibility change in the pulvinar of the thalamus and hippocampus. This suggests that there may be region-specific alterations of calcium deposition in cognitively impaired subjects with DM. [ABSTRACT FROM AUTHOR]

Background: Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy.Objective: We investigated that dementia with RBD might show distinctive cortical atrophic patterns.Methods: A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects.Results: Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes.Conclusion: The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy. [ABSTRACT FROM AUTHOR]

The insular cortex is associated with neuropsychiatric symptoms, changes in cardiovascular and autonomic control, and mortality in Alzheimer’s dementia. However, the insular cortex does not provide information on the contribution of the other cortices to cognitive decline. We hypothesized that the factors that affect to atrophy in insular cortex are different from other cortical regions. A total of 42 patients with probable Alzheimer’s dementia were included in the analyses. The manual drawing of regions of interest was used to detect insular cortex located in the deep gray matter and to avoid coatrophy. Covariates, which could affect to the atrophy of the cerebral cortex, were selected based on previous studies. Any of the demographic factors, vascular risk factors, and the severity scales of dementia was not associated with any insular volume ratio. We suggest that the pathomechanisms of atrophy in insular cortex are different from those of other cortex regions in Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is a devastating illness that results in progressive cognitive decline and neuropsychiatric symptoms. The neuropsychiatric symptoms are associated with a rapid decline in cognition and activities of daily living and increased mortality, however the neuroanatomical localisation involved in the development of neuropsychiatric symptoms remains poorly understood. The aim of this study was to identify the association with the regional volume of the insular cortex and each neuropsychiatric symptom in patients with AD. Methods: Subjects diagnosed with AD (n = 40) were evaluated. Magnetic resonance images were obtained and the insular cortex was subdivided into four subregions through the central sulcus of the insula and bilaterally: right anterior insular cortex, right posterior insular cortex, left anterior insular cortex and left posterior insular cortex. The neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A partial correlation analysis was performed. Results: A significant negative correlation existed between apathy, the irritability subscale score and the volume ratio of the bilateral anterior insular cortex and right posterior insular cortex (r = -0.457, -0.433 and -0.572, respectively, p = 0.032, 0.044 and 0.005, respectively). Conclusion: The findings suggest that the regional atrophy of the insular cortex is associated with neuropsychiatric symptoms in AD patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to evaluate the relationship between loss of white matter cholinergic pathways, atrophy of the nucleus basalis of Meynert (NBM), and cognitive function in patients with subcortical ischemic vascular dementia (SIVD) or Alzheimer's disease (AD). METHODS: The participants included 26 SIVD, 17 probable AD with or without white-matter changes, and 20 age-matched healthy controls. Thin-section coronal T2-weighted images were acquired using 3.0 T MR. The extent of white matter hyperintensities within cholinergic pathways were assessed using the cholinergic pathways hyperintensities scale (CHIPS). NBM atrophy was assessed from the thickness of the substantia innominata (SI) at the level of the crossing of the anterior commissure. Cognitive impairment was measured using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Correlations between CHIPSs, SI thickness, and cognitive impairment were evaluated using the Spearman ranked correlation test. RESULTS: In AD, MMSE scores and CDR were correlated with SI thickness (ρ = 0.450, p = 0.006 and ρ = -0.520, p = 0.030, respectively) but not with CHIPS scores (ρ = -0.160, p = 0.530 and ρ = 0.270, p = 0.292, respectively). By contrast, aggravated MMSE score and CDR in SIVD had a tendency to correlate with elevated CHIPS scores (ρ = -0.344, p = 0.127 and ρ = 0.521, p = 0.021, respectively) but not with SI thickness (ρ = -0.210, p = 0.480 and ρ = 0.080, p = 0.736, respectively). CONCLUSIONS: Loss of cholinergic pathways correlates with cognitive dysfunction in both AD and SIVD. The mechanisms appear to differ: NBM atrophy is likely to be the predominant contributor to cognitive impairments in AD, whereas, the cognitive dysfunction of SIVD was associated with compromised subcortical cholinergic fibers not with nucleus itself. [ABSTRACT FROM AUTHOR]